Hhma

[serotonin2A]

The metabolite isn't intend to be excreted because it isn't a xenobiotic compound. That compound, dopamine, is endogenous and so there is a wholly different regulatory system for that and like neurotransmitters.

I don't think you can really distinguish the action of COMT on dopamine versus exogenous catecholamines. Xenobiotic compounds with catechol groups can also be metabolized by COMT.

 

[aced126]

Hmm, ok, but that's not what the enzyme was designed for. If a compound is by chance a substrate at that enzyme then yeah it'll be metabolised to a more lipophilic metabolite, but this isn't intended. CYP enzymes on the other hand intend to metabolise a wide range of substrates to more polar metabolites.

 

[Dresden]

Out of curiosity, how do the log P's of these two measure up:

Warning: Do not use until adequate safety profiles have been established empirically.

 

[aced126]

The logPs (octan-1-ol/water partition ratio) of all these compounds will be less than that of amphetamine. LogP will reduce in second compound. The reason why logP increases in the case of heroin is that there are 2 hydroxy groups there already (this brings down logP). Acetylating these groups increases logP relatively. However, compare 6-monoacetlylmorphine (logP=1.9 http://www.drugbank.ca/metabolites/DBMET01172) to desomorphine (logP=2.5 http://www.drugbank.ca/drugs/DB01531).

In fact, very roughly speaking, each acetyl group added onto the ring decreases logP by about 0.6 (benzene logP =2.13, phenylacetate logP predicted =1.55).